In the initial stage of disease, to provide a suitable medical treatment for a disease, precise and prompt detection of morphological change of organ and tissue which has been caused in organism by the disease is desired through a simple method. Specifically in cases when treating cancer, it is essential for early treatment to specify the lesion region in the initial stage of carcinogenesis to definitely determine its size. Commonly known medical treatments for this purpose include, for example, living organ examination using an endoscope and imaging diagnosis such as radiography, MRI and sonography.
Living organ examination, whereby the lesion region can be directly observed, is effective for diagnostic definition; however, it is painful procedure for an examinee. Radiography or MRI exposes an examinee to radiation rays or a magnetic field potentially harmful to the human body, and when tracing the focus or lesion region with the elapse of time, the exposure time increases in proportion to the tracing time. In the measurement for MRI diagnosis, the photographing time is generally long and noises generated by the MRI photographing apparatus gives an examinee mental pressure. In addition, its facility and apparatus are large and require a large amount of labor and the cost for installation and operation is high.
On the other hand, light is a means capable of performing noninvasive diagnosis of organs using a relatively simple apparatus. There have been practically used, for example, a clinical thermometer in which the temperature of an infant is measured by detection of infrared rays emitted from the eardrum, a device for diagnosis for neonatal jaundice by numerical evaluation of the yellowing degree of bilirubin deposited onto subcutaneous tissue, a pulse oximeter for noninvasive measurement of aerated blood oxygen saturation (SaO2) based on the degree of light absorption, and endoscopical observation of auto-fluorescence, employing the characteristic that auto-fluorescing of oncocyte is less than that of a normal cell (being excited at 450 nm and fluorescing at 520 nm). However, there is raised the problem that many hemoglobins exhibiting absorption in the visible region exist in organs and only information of the outermost surface of organ can be measured or collected.
In the near-infrared region at the wavelengths slightly longer than visible light, absorption of the respective substituents having a hydrogen bond occurs but such absorption is relatively small so that near-infrared rays are easily transmitted through tissue. It is contemplated that employing such characteristics of near-infrared rays make it feasible to measure bio-information without loading a useless load onto the body. However, light is strongly scattered by tissue so that it is generally not easy to know through which portion of the organ detected light has passed or from which portion information is transmitted. Recently, information of the deep portion of the body can also be obtained by combinations of a high-sensitive sensor, a laser generating extremely short pulses and simulation for internal light scattering employing Monte Carlo method.
There is noted fluorescent photography as a diagnostic method using near-infrared rays, in which near-infrared dyes are injected into a tumor portion to image the tumor portion. In this method, a compound capable, as a contrast medium, of fluorescing upon exposure to exciting light at wavelengths in the near-infrared region is dosed into a live body. Then, exciting light of near-infrared wavelengths is irradiated from outside the body and detection of emitted fluorescence from the fluorescent contrast medium concentrated at the tumor portion provides definite decision of the lesion portion.
There is known, as such a fluorescing contrast medium, indocyanine green which has been confirmed to be safe within a living body. It is said that veins in tumor portions are randomly open and close, causing retention of bloodstreams (so-call blood pool). When the indocyanine green is dosed to an animal exhibiting a tumor, the retention time of blood differs between the normal portion and the tumor portion (i.e., the indocyanine green is promptly discharged from the tissue comprised of normal cells), so that irradiation of exciting light at the wavelengths in the near-infrared region can cause the tumor portion to come out (Ohata et al., Basic Study of Cancer Diagnosis Using Indocyanine Green and Near-Infrared Topography in Rat Experiment Tumor, Nippon Ihokaishi, 62 (6), 284-286, 2002).
Since fluorescing contrast medium of cyanine type compounds was reported, there have been disclosed techniques using various peripheral cyanine type compounds as a contrast medium to achieve modification into a compound exhibiting enhanced hydrophilicity, molar absorption coefficient and quantum yield, as described in JP-A No. 2000-95758, 2002-526458, 2003-517025, 2003-160558 and 261464 (hereinafter, the term, JP-A refers to unexamined Japanese Patent Application Publication). In addition to resolving performance (imaging power) capable of discriminating lesion tissue from normal tissue, the medium needs to completely decomposed to be nontoxic or be completely discharged after imaging (non-accumulativeness). However, there has not been found any safer compound providing both of the foregoing or any other contrast medium containing the said compound.